Adrenergic Agonists and the Sympathetic Nervous System

• Sympathomimetic drugs activate the sympathetic nervous system (SNS)
• Adrenergic agonists are used in conditions like cardiac arrest, hypotension, asthma, and anaphylaxis

Adrenergic Receptor Sites & Responses

• Alpha1 receptors cause vasoconstriction (↑ BP) and pupil dilation (mydriasis)
• Beta1 receptors increase heart rate and contractility, used in heart failure and shock
• Beta2 receptors cause bronchodilation and relaxation of uterine muscles, useful in asthma and preterm labor

Monitoring and Assessment

• Assess heart rate, blood pressure, oxygenation, and for arrhythmias when using adrenergic agonists

Direct vs. Reflex Cardiac Effects

• Beta1 agonists increase HR/contractility directly
• Baroreceptor reflex may counteract effects by lowering HR in response to BP changes

Epinephrine for Anaphylaxis

• Epinephrine is the drug of choice for anaphylaxis
• It causes vasoconstriction (↑ BP), bronchodilation, and inhibits histamine release

Adrenergic Antagonists

Alpha- & Beta-Blockers

• Alpha blockers cause vasodilation and treat HTN and BPH
• Beta blockers decrease HR and contractility, treat angina, HTN, and arrhythmias

Adverse Effects

• Alpha blockade can cause hypotension and reflex tachycardia
• Beta blockade can cause bradycardia and bronchoconstriction, avoid using in asthma

Cardioselective Beta-Blockers

• Cardioselective Beta-Blockers (Beta1 Selective) are safer to use in patients with respiratory disease

Indirect-Acting Antiadrenergic Agents

Alpha2 Agonists

• Alpha2 Agonists (Methyldopa, Clonidine) cause ↓ sympathetic outflow, resulting in ↓ BP

Rebound Hypertension

• Rebound hypertension with clonidine occurs with sudden discontinuation
• Tapering off the drug gradually will avoid this adverse effect

Diuretics

Diuretic Selection Factors

• Diuretic selection depends on efficacy, dose-response, and potential drug interactions

Types & Cautions

• Thiazides cause mild diuresis, but should be avoided in renal failure
• Loop diuretics are potent and used for HF/edema, but carry a risk of hypokalemia
• Combination therapy often involves using K+-sparing diuretics

RAAS Drugs

ACE Inhibitors

• ACE inhibitors cause ↓ BP and prevent sodium retention, but are contraindicated in pregnancy

ARBs vs. ACEIs

• ARBs do not cause cough, but have similar BP effects as ACE inhibitors

Aldosterone Antagonists

• Aldosterone antagonists carry a risk of hyperkalemia, and should be used with caution in patients with CKD

Calcium Channel Blockers (CCBs)

• Beta receptors and calcium channels are linked via intracellular signaling
• They affect heart rate and contractility

CCB Types

• Dihydropyridines (Nifedipine) act on vasculature and cause less cardiac depression
• Verapamil/Diltiazem affect the heart & vessels, can increase risk of bradycardia
• Drug interactions: avoid beta-blockers to prevent excessive cardiac depression

Vasodilators

Selectivity effects

• Arterial dilation (Hydralazine) ↓ afterload, and ↑ HR as a reflex

Adverse effects

• Adverse effects include reflex tachycardia and edema

Hypertension

JNC8 Guidelines

• Selection is based on comorbidities

Drug therapy principles

• Titrate dose versus adding a second agent.

HTN emergencies

• Commonly treated with Nitroprusside and labetalol

Pregnancy HTM Agents

• Methyldopa and labetalol are safer in pregnancy

Heart Failure

Key Drug Classes

• RAAS Inhibitors and Beta-Blockers improve survival
• Diuretics and Vasodilators are for symptom relief
• Digoxin improves contractility but can be toxic
• Low K+ increases Digoxin toxicity risk

Antidysrhythmic Drugs

Drugs causing heart block

• Beta-blockers, CCBs, and Digoxin can cause heart block

Vaughan Williams Classification

• Drugs are categorized by its mechanism of action

Amiodarone

• Used for AFib/Ventricular arrhythmias, but may damage lungs and liver

Lipid-Lowering Drugs

First-Line treatment

• Statins (HMG-CoA inhibitors) are a first line treatment for hypercholesterolemia

Rhabdomyolysis

• Rhabdomyolysis is a rare but severe muscle breakdown, statin induced

Comparison of Drug Classes

• Statins block cholesterol synthesis
• Fibrates lower triglycerides
• Bile Acid Sequestrants bind bile acids, increase cholesterol excretion

Angina

Types and Treatments

• Stable Angina is due to demand so treat with nitrates and beta-blockers
• Variant Angina is due to vasospasm so treat with CCBs
• Unstable Angina is emergent so treat with antiplatelets, anticoagulants

Organic Nitrates

• Vasodilation and ↓ preload, increasing the risk of hypotension

Anticoagulants & Thrombolytics

Drug Types & Effects

• Anticoagulants (Warfarin, Heparin) prevent clot formation
• Antiplatelets (Aspirin, Clopidogrel) prevent platelet aggregation
• Thrombolytics (tPA) breaks down existing clots

Warfarin vs. Heparin

• Warfarin is taken orally, has a slow onset, and requires INR monitoring
• Heparin is given IV/SC, has a rapid onset, and requires aPTT monitoring

STEMI Management

Acute Drug Therapy

• Treat with Morphine, Oxygen, Nitrates, Aspirin (MONA)

Reperfusion therapy

• tPA, PCI

Post-MI Drugs

• Beta-blockers, ACEIs and antiplatelets prevent the reoccurrence of MI

Adrenergic drugs overview

Adrenergic drugs

• Adrenergic drugs target the sympathetic nervous system (SNS)
• They act on adrenergic receptors; Alpha (α) and Beta (β)
• Main neurotransmitters are Epinephrine, norepinephrine, and dopamine

Adrenergic Receptors and Effects

• Alpha 1 receptors are located in blood vessels, causing vasoconstriction and ↑BP
• Alpha 2 receptors are located in the CNS (presynaptic), inhibiting norepinephrine which in turn causes vasodilation and ↓BP
• Beta 1 receptors are located in the heart causing ↑ HR, ↑ Contractility
• Beta 2 receptors are located in the lungs and muscles causing bronchodilation and vasodilation

Adrenergic Agonists (Sympathomimetics)

Alpha 1 Agonists

• These are vasoconstrictors
• Examples of Alpha 1 agonist drugs are Phenylephrine, Epinephrine, Norepinephrine, and Dopamine (high doses)
• used to treat hypotension and shock by increasing BP

Other uses of Adrenergic Agonists

• Hemostasis (vasoconstriction)
• Nasal decongestion
• Adjunct to local anesthesia
• Mydriasis (pupil dilatation)

Main Alpha 2 Agonists

• Treats hypertension (HTN), ADHD, Pain, panic disorders, glaucoma, and sedation
• Examples of Alpha 2 Agonist are Clonidine (HTN, ADHD), Methyldopa (HTN in pregnancy), Guanfacine (ADHD)
• They work by inhibiting SNS activity (sympatholytic); ↓ norepinephrine release → Vasodilation and ↓BP

Adverse effects

• Hypertension (HTN)
• Necrosis with extravasation
• Bradycardia (due to baroreceptor reflex)

Contraindications

• Hypertension
• Bradycardia
• Prostatic Hyperplasia (BPH)

Adverse Effects of Alpha-2 Agonists

• Sedation, dry mouth
• Rebound HTN if stopped abruptly, must wean over 2-4 days
• Nausea, GI upset
• Risk for abuse - main drug is Clonidine

Epinephrine

• Epinephrine is the ultimate adrenergic agonist
• Activates all adrenergic receptors (a1, a2, β1, β2) and is the drug of choice for anaphylaxis
• Alpha 1 Activation causes Vasoconstriction and ↑ BP
• Beta 1 Activation causes ↑ HR, restores cardiac function (V-fib, asystole)
• Beta 2 activation causes Bronchodilation (for asthma and anaphylaxis) ---Epinephrine cannot be given orally because it has a rapid metabolism

Beta Agonists vs Beta 1 Agonists

• Beta 1 Agonists (Cardio-selective) includes Dobutamine and Isoproterenol

Beta 2 Agonists examples

• Albuterol (asthma and COPD)
• Terbutaline (preterm labor)

Beta 2 Agonists mechanism

• Bronchodilation (asthma, COPD)
• Vasodilation (muscles and liver)
• Relax uterine muscles (delays labor)

Beta 2 Agonists adverse effects

• Tremors and axiety
• Headaches and palpitations ---In high doses, can activate ẞ1 → tachycardia!

Adrenergic antagonists (blockers)

Alpha 1 Antagonists (blockers)

• Alpha 1 Antagonists (blockers) are rarely used for HTN
• Alpha 1 Antagonists (blockers) are used for Benign Prostatic Hyperplasia (BPH) and for Urinary retention (BPH, bladder issues)
• --Note: Tamsulosin (for BPH and urinary retention

Therapeutic uses

• Treats Hypertension (not first-line)

Beta Blockers examples

• Selective (β1 only): Metoprolol, Atenolol and Esmolol
• Non-selective (β1 & β2): Propranolol and Nadolol

Beta Blockers mechanism

↓HR, ↓ contractility useful for Angina + is a negative inotrope ↓O2 demand Suppresses Social Network Service SNS activation

Beta Blockers therapeutic uses

HTN, Angina Post-MI (reduces mortality) Heart failure (metoprolol, carvedilol) Arrhythmias

Renin

• Released from juxtaglomerular cells of the kidney in response to decline in BP, blood volume, plasma sodium, renal perfusion pressure, or beta 1 stimulation → catalyzes formation of angiotensin I from angiotensinogen in the blood

Angiotensin-Converting Enzyme (ACE)

• Catalyzes conversion of angiotensin I to angiotensin II is abundant in the vasculature of the lungs

Angiotensin II

• vasoconstriction increases BP→ stimulates aldosterone release
• Cardiovascular effects: hypertrophy, remodeling, increases vessel walls, and thickens intimate surface of vessels

Aldosterone

• promotes retention of sodium and water , and excretion of potassium Also CV effects: cardiac remodeling & fibrosis, activates the SMS

Blood Pressure Regulation

• ↓Renal perfusion, and ↓BP → Renin release → Angiotensin II → Vasoconstriction, and ↑ BP
• Angiotensin II also promotes Aldosterone → increasing Na+/H2O retention → and in turn Increasing BP

HTN treatment

• ACE Inhibitors (ACEIs) --Angiotensin Receptor Blockers (ARBs)
• Thiazide Diuretics -- Calcium Channel Blockers (CCBs)

Medication choice depends on

• Comorbidities ( Diabetes, CKD, and Heart Failure), any Special populations (elderly, black patients, and Pregnant women). Multidrug therapy requirements

Mechanism of Action for Diuretics

• Blocks Na+ & Cl- absorption which increases urine
• Most Potent for Proximal tubule
• Reduces Preload and Afterload Class 1
• Loop Diuretics-most potent Class 2
• Thiazide Diuretics Class 3
• Osmotic Diuretics Class 4
• Potassium-Sparing Class 5
• Carbonic Anhydrase Inhibitors

RAAS System & Related Drugs

ACE Inhibitors

Example: Lisinopril

Mechanism

• prevents Angitotensin II formation, ↓ Vasoconstriction and ↓ Aldosterone →↓ BP

Therapeutic Uses

• HTN, Heart Failure, Myocardial Infarction, and prevents CV events

HTN medication: selection and side effects

64 y/o, BP 155/90, GFR 70? → Thiazide

• (HCTZ/Chlorthalidone) (First-line for HTN)

New medication may cause these effects in some patients

• Report extreme Dizziness
• near-syncope in many BP medications

Diuretics

• Potassium is key for function
• Diuretics deplete potassium
• Encourage foods such as bananas/citrus

Digoxin & Potassium

• Low potassium is associated with increased binding and toxicity

• --More dig, less k+

• High Potassium=Less Digoxin

• --Important Notes New BP Medication = Diltiazem (CCB) + Isosorbide mononitrate (Nitrate)

Heparin and Enoxaparin

• Enoxaparin is a low molecular weight heparin
• Can cause bleeding ( watch for low BP, high HR for signs of blood loss)

If Patient is hemorrhaging

• Stop heparin
• Give protamine solution

Ischemic stroke

• Give tPA
• Ischemic stroke is caused by clots; therefore need to give something that will break it up

Lab side effects from new Warfarin

• Report headache, stomach discomfort, and bloody stools
• -Important note to consider, warfarin (Coumadin) will be stopped because the nose bleed has been uncontrolled

Thrombi

• Plavix is used for arterial thrombi preventation

Adrenergic agonists mimic the sympathetic nervous system, affecting alpha and beta receptors. Alpha1 activation results in vasoconstriction. Beta1 agonists increase heart rate and contractility while Beta2 agonists cause bronchodilation. Epinephrine is essential for anaphylaxis due to its vasoconstrictive and bronchodilatory effects.